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SUMMARY
Nasal gland salt secretion and plasma corticosteroid concentrations in wing venous plasma were measured at 15 min. intervals after intravenous loading of male ducks (Anas platyrhynchos) with 154 mm- or 500 mm-NaCl and gulls (Larus argentatus) of undetermined sex with 500 mm-NaCl. Plasma corticosteroids were measured by fluorimetry, Na+ and K+ in nasal fluid by flame photometry, and changes in plasma volume of the duck by dye dilution. Age and/or seasonal variations in plasma corticosteroid concentrations were observed in the duck. Corticotrophin (10 i.u./kg. in the duck and 20 i.u./kg. in the gull) caused a progressive rise in plasma corticosteroid concentrations in both species. The nasal glands began to secrete in both species within 15 min. after loading with 500 mm-NaCl but in the gull the secretion rate reached a peak earlier and declined more rapidly. Although no clear relationship between adrenocortical and nasal gland functions was found in either species, comparison of changes in plasma corticosteroid concentrations and plasma volume in the duck under both conditions of saline loading supported this connexion.
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Corticosteroid feedback mechanisms were investigated at the hypothalamic level using the rat hypothalamus in vitro and at the pituitary level using basal hypothalamic-lesioned rats. Both fast and delayed corticosteroid feedback effects were demonstrated at the level of the hypothalamus and pituitary gland with doses of corticosteroids within or near the physiological range. These two phases of feedback were separated temporally by a 'silent period' during which no feedback was apparent.
Studies on the mechanism of action of corticosteroids at the hypothalamic level showed that the fast feedback mechanism acts by inhibition of release whilst the delayed feedback mechanism acts by inhibition of both synthesis and release. The fast feedback action of corticosterone does not appear to act by excitation of neuroinhibitory pathways since neither picrotoxin nor phentolamine prevented the feedback action of corticosteroids in vitro.
Corticosterone inhibition of corticotrophin releasing factor release was overcome by depolarization of the membrane with K+ suggesting that the mechanism of action of the fast feedback of corticosteroids is by membrane stabilization.
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Clinique Endocrinologique, C.H.U. La Timone, Marseille 13385, France
(Received 23 September 1975)
Melanocyte-stimulating hormone (MSH) and adrenocorticotrophin (ACTH) release vary independently in the rat following corticosteroid administration or adrenalectomy as shown by bioassay (Kastin, Schally, Viosca & Miller, 1969; Dunn, Kastin, Carrillo & Schally, 1972; Thody & Hinks, 1973) or radioimmunoassay (Usategui, Oliver, Vaudry, Lombardi, Mourre, Rozenberg & Vague, 1975; Usategui, Oliver, Vaudry, Lombardi, Rozenberg & Mourre, 1976) methods. In an attempt to define more clearly the effect of corticosteroids on the release of α-MSH and ACTH, plasma α-MSH and ACTH have been measured after stimulation by haloperidol injection or ether stress in normal as well as in corticosteroid-treated male rats. Immunoreactive α-MSH has been used as an index of MSH activity because α-MSH is thought to be the major MSH in the rat (Baker, 1973; Scott, Lowry, Ratcliffe, Rees & Landon, 1974; Thody, Penny & Clark, 1975).
Adult male
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The role of the foetal adrenal cortex in the initiation of parturition in the sheep is well established; however the evidence for a similar role by the human foetal adrenal is circumstantial and based upon the association of prolonged gestation with foetal adrenal hypoplasia (Anderson, Laurence & Turnbull, 1969; Roberts & Cawdery, 1970) and of premature delivery with foetal adrenal hyperplasia (Anderson, Laurence, Davies, Campbell & Turnbull, 1971). There is no information concerning changes in levels of corticosteroids in the human foetus in late pregnancy and the present study was undertaken in order to examine the relationship of umbilical cord arterial and venous plasma concentrations of corticosteroids at the time of delivery to gestational age of the foetus and type of labour.
Matched samples of umbilical cord arterial and venous blood were collected during December 1971 — January 1972. Plasma levels of corticosteroids were determined by a competitive protein-binding technique (Murphy,
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In the cow, a single injection of adrenocorticotrophic hormone (ACTH) was found to produce a rapid rise in plasma 17:21-dihydroxy-20-keto-corticosteroids, and then an equally rapid fall. This was followed by a more gradual fall to pre-injection levels which were reached within 24–48 hr of the start of the experiment. The presence of cortisol in the blood samples was confirmed by chromatographic examination. Detectable amounts of other corticosteroids were not found.
The ACTH injections produced a very definite fall in milk yield. Return to generally steady levels took 3 days in one case and more than 7 days in another.
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Free fatty acids (FFAs) are rapidly mobilized by ACTH and have been shown to be potent endogenous modulators of steroid-protein interactions. We increased FFA in lagomorphs by ACTH and then separated the transient increase in glucocorticoid binding capacity of plasma into that accounted for by changes in binding to albumin and to corticosteroid-binding globulin (CBG). Sequential injections of dexamethasone and ACTH into both snowshoe hares and laboratory rabbits resulted in the rapid mobilization of FFA only after the ACTH injection. The maximum corticosteroid binding capacity increase paralleled that of the FFA increase in both species. In rabbits, CBG levels remained constant over the duration of the experiment. Corticosterone binding by rabbit albumin increased in a dose-dependent fashion in response to increases in FFA (oleic and linoleic acid) concentrations. Finally, by stimulating FFA release in snowshoe hares with ACTH and separating the increase in corticosteroid binding capacity through selective denaturing of CBG by heat, we determined that the increase in plasma binding capacity was a response to changes in binding by albumin, not CBG. Thus FFA released in response to stressors in lagomorphs may effect short-term increases in steroid binding.
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Assay of corticosteroids in the plasma of guinea-pigs showed that concentrations were higher in lactating than in non-lactating and male animals. In five isolated perfused mammary gland experiments in which corticosteroids were at concentrations of 1·3–3·0 μg/ml in the perfusate, equivalent to concentrations during lactation, the mean (±s.e.m.) uptake by the mammary gland was 900 ± 210 ng g−1 h−1. In five experiments in which the concentrations of corticosteroid in the perfusate were 190–580 ng/ml, the uptake by the mammary gland was significantly lower (316 ± 73 ng g−1 h−1; P < 0·05). For the ten experiments there was a significant correlation between the concentration of corticosteroid in the perfusate and uptake by the mammary gland (P < 0·05). No convincing evidence for a galactopoietic role of corticosteroids in the guinea-pig was obtained, although administration of cortisol significantly stimulated the uptake of glutamine by the perfused gland.
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SUMMARY
Peripheral blood corticosteroid levels were determined in nine species of Australian marsupial (Eastern grey kangaroo, black-tailed, Bennett's and pademelon wallabies, quokka, wombat, koala and Western native and tiger cats), one species of monotreme (echidna) and one placental Australian mammal (dingo). Animals were obtained or bled with minimal disturbance and came from areas considered to have adequate sodium content of the vegetation. Aldosterone, corticosterone, cortisol, 11-deoxycorticosterone and 11-deoxycortisol were measured and levels found to be similar to five introduced eutherian species (sheep, cow, dog, fox and man) with the exception of the koala and the wombat. Cortisol was the predominant corticosteroid, except in the koala, which produced corticosterone in relatively the greatest quantity, and the wombat which produced more 11-deoxycortisol. Steroid levels were generally low in the wombat. ACTH administered to the koala changed its pattern of corticosteroid secretion from predominantly corticosterone to cortisol. In the dingo, administration of ACTH caused rises in corticosteroid levels similar to those seen in most other eutherian mammals.
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1. An examination has been made of the free and glucuronide-conjugated corticosteroids in the plasma of normal controls and of patients before and after hypophysectomy. Quantitative measure of the free plasma corticosteroid level 72 hr after withholding cortisone from a hypophysectomized patient (cortisone withdrawal test) is a useful index of completeness of hypophysectomy. Qualitative examination failed to detect corticosteroids in these patients.
2. In all plasmas examined (controls and patients in resting state and after adrenocorticotrophic hormone (ACTH)) the main component of the free corticosteroid fraction is cortisol. In 50% of the plasma samples cortisone was detected. Even after ACTH only occasional traces of corticosterone were detected by the method used in this study.
3. In the glucuronide-conjugated fraction of plasma from subjects in the resting state three compounds, concluded to be tetrahydrocortisol (THF)†, tetrahydrocortisone, and allo-THF†, were regularly seen. After ACTH other material was detected in this fraction which is considered to be tetrahydrocorticosterone (THB), tetrahydro 11-deoxycortisol (THS) and allo-THB. Administration of oral cortisone to hypophysectomized patients did not increase the amounts of THB, THS or allo-THB in the plasma.
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SUMMARY
Exposure of newborn Holstein and Jersey calves to −4 °C did not significantly increase the plasma corticosteroids (cortisol and corticosterone) concentrations compared with calves kept at 16 °C. Two Holstein calves exposed to −12 °C showed a slight decrease of plasma corticosteroid concentrations and one Holstein calf at −18° C responded with a marked increase in both hormones during cold exposure. In the animals at 16 and −4 °C the plasma cortisol and corticosterone concentrations fell steadily during the sampling period. There was also a marked, and almost linear, decrease in the packed cell volume during the sampling period; this occurred in all groups. That this was not due entirely to the withdrawal of blood was shown by a similar decrease in two calves from which only small quantities of blood had been taken. Thus, the decrease in plasma corticosteroids may have resulted to some extent from haemodilution.
An increase in glucose concentration was observed in both the control and cold-exposed calves. There was no correlation between the changes in plasma glucose and plasma corticosteroids.